The main objectives of this project are: (1) to determine whether DES is metabolized to biologically and hormonally active metabolites; (2) to test the hypothesis that certain chemicals are "transplacental toxicants" due to their relative binding to plasma/receptor proteins particularly alpha-fetoprotein; (3) to investigate some of the biochemical mechanisms which contribute to effects of prenatal exposure of mice to hormonally active environmental chemicals; (4) to investigate the mechanism of uterine hormonal responsibeness by assessing the nucleic acid and protein synthetic activity; (5) to determine the role of growth factors in hormonal stimulation and to define the molecular loci of transplacental toxicity using structure-function relationships of different environmental chemicals; and (6) to determine biochemical markers for transplacental toxicity. These objectives are approached using refined biochemical techniques of hormone receptors and hormone action. The basic physiological effects on hormone synthesis and hormone levels will be studied using chemical extraction techniques and radioimmunoassays. The carcinogenic and toxic nature of hormonally active environmental chemicals will be studied in vivo.